Agents and Actions

, Volume 34, Issue 1–2, pp 274–277 | Cite as

Structural and functional organization of the human neutrophil 60 kDa bactericidal/permeability-increasing protein

  • C. E. Ooi
  • J. Weiss
  • P. Elsbach
C. Gordon van Arman Scholarship Competition (Finalists)


We have isolated, after limited proteolysis of the bactericidal/permeability-increasing protein (BPI) of human polymorphonuclear leukocytes (PMN), two fragments representing roughly the two halves of the BPI molecule. The 25 kDa N-terminal fragment possesses all the antibacterial activities of the 60 kDa parent protein, while the ca. 30 kDa C-terminal fragment has no detectable activity. The 25 kDa fragment is as potent on a molar basis as holo-human BPI against roughEscherichia coli, is more potent than holo-BPI against more resistant smoothE. coli, and retains the specificity of BPI toward Gram-negative bacteria. The findings suggest that all of the molecular determinants of the antibacterial properties of BPI reside within the N-terminal half of the molecule, implying a novel structural/functional organization for a cytotoxic protein.


Antibacterial Activity Human Neutrophil Antibacterial Property Polymorphonuclear Leukocyte Functional Organization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    P. Elsbach,Trends in biotechnology, 8, 26–30 (1990).CrossRefPubMedGoogle Scholar
  2. [2]
    P. Elsbach and J. Weiss,In inflammation: Basic principles and clinical correlates (Eds. J. L. Gallin, I. M. Golstein and R. Snyderman), pp. 445–470, Raven Press (1988).Google Scholar
  3. [3]
    J. E. Gabay et al.,Antibiotic proteins of human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci., USA86, 5610–5614 (1989).Google Scholar
  4. [4]
    J. Weiss, P. Elsbach, I. Olsson and H. Odeberg,Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J. Biol. Chem.253, 2664–2672 (1978).PubMedGoogle Scholar
  5. [5]
    P. Elsbach, J. Weiss, R. C. Franson, S. Beckerdite-Quagliata, A. Schneider and L. Harris,Separation and purification of a potent bactericidal/permeability-increasing protein and a closely associated phospholipase A2 from rabbit polymorphonuclear leukocytes. J. Biol. Chem.254, 11000–11009 (1979).PubMedGoogle Scholar
  6. [6]
    B. A. Mannion, J. Weiss and P. Elsbach,Separation of sublethal and lethal effects of the bactericidal/permeability-increasing protein on Escherichia coli. J. Clin. Invest.85, 853–860 (1990).PubMedGoogle Scholar
  7. [7]
    C. E. Ooi, J. Weiss, P. Elsbach, B. Frangione and B. A. Mannion,A 25 kDa NH 2-fragment carries all the antibacterial activities of the human neutrophil 60 kDa bactericidal/permeability-increasing protein. J. Biol. Chem.262, 14891–14894 (1987).PubMedGoogle Scholar
  8. [8]
    B. A. Mannion, E. S. Kalatzis, J. Weiss and P. Elsbach,Preferential binding of the neutrophil granule-derived bactericidal/permeability-increasing protein to target bacteria. J. Immunol142, 2807–2812 (1989).PubMedGoogle Scholar
  9. [9]
    U. K. Laemmli,Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227, 680–685 (1970).PubMedGoogle Scholar
  10. [10]
    O. H. Lowry, N. J. Rosenbrough, A. L. Farr and R. J. Randall,Protein measurement with the Folin phenol reagent. L. Biol. Chem.193, 265–275 (1951).Google Scholar
  11. [11]
    P. W. Gray, G. Flaggs, S. R. Leong, R. J. Gumina, J. Weiss, C. E. Ooi and P. Elsbach,Cloning of the cDNA of a human neutrophil bactericidal protein. J. Biol. Chem.264, 9505–9509 (1989).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1991

Authors and Affiliations

  • C. E. Ooi
    • 1
  • J. Weiss
    • 1
  • P. Elsbach
    • 1
  1. 1.Departments of Medicine and MicrobiologyNew York University School of MedicineNew York

Personalised recommendations